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RNA-based therapies in liver metabolic diseases
被引:0
作者:
Fontanellas, Antonio
[1
,2
,3
]
Berraondo, Pedro
[3
,4
,5
]
Urigo, Francesco
[1
]
Jerico, Daniel
[1
]
Martini, Paolo G., V
[6
]
Pastor, Fernando
[7
]
Avila, Matias A.
[2
,3
,8
]
机构:
[1] Univ Navarra, Solid Tumors Program, Hepatol Porphyrias & Carcinogenesis Lab, CIMA,CCUN, Pamplona, Spain
[2] Ctr Invest Biomed Red, CIBEREHD, Area Enfermedades Hepat & Digest CIBERehd, Madrid, Spain
[3] Inst Invest Sanitarias Navarra IdiSNA, Pamplona, Spain
[4] Univ Navarra, Immunol & Immunotherapy Program, CIMA, CCUN, Pamplona, Spain
[5] Ctr Invest Biomed Red, Area Oncol, CIBERonc, Madrid, Spain
[6] ReAlta Life Sci, Norfolk, VA USA
[7] Univ Navarra, Mol Therapeut Program, CIMA, CCUN, Pamplona, Spain
[8] Univ Navarra, Solid Tumors Program, Hepatol Lab, CIMA,CCUN, Pamplona, Spain
关键词:
LIVER METABOLISM;
GENE THERAPY;
DRUG DEVELOPMENT;
MOUSE MODEL;
THERAPEUTICS;
PATHOGENESIS;
DELIVERY;
D O I:
10.1136/gutjnl-2023-331742
中图分类号:
R57 [消化系及腹部疾病];
学科分类号:
摘要:
RNA-based therapeutics have rapidly emerged over the past decade, offering a new class of medicines that differ significantly from conventional drugs. These therapies can be programmed to target or restore defective genes, allowing for more personalised treatments and reducing side effects. Notably, RNA therapies have made significant progress in the treatment of genetic liver diseases, exemplified by small interfering RNA treatments for hereditary transthyretin amyloidosis, which use liver-targeting strategies such as GalNAc conjugation to improve efficacy and safety. RNA-based gene-editing technologies, such as base editor and prime editor clustered regularly interspaced short palindromic repeats systems, also show promise with their ability to minimise genomic rearrangements and cancer risk. While RNA therapies offer high precision, challenges remain in optimising delivery methods and ensuring long-term safety and efficacy. Lipid nanoparticle-mRNA therapeutics, particularly for protein replacement in rare diseases, have gained support from preclinical successes. Compared with viral gene therapies, mRNA therapies present a safer profile with reduced risks of genomic integration and oncogene activation. However, clinical trials, especially for rare diseases, face limitations such as small sample sizes and short observation periods. Further preclinical studies, including non-human primates, will be essential for refining trial designs. Despite their potential, the high costs of RNA therapies pose a challenge that will require cost-utility models to guide pricing and accessibility. Here, we discuss the fundamental aspects of RNA-based therapeutics and showcase the most relevant preclinical and clinical developments in genetic liver metabolic diseases.
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页数:14
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